A clear need exists for improved treatment of solid tumor forms of cancer. Radiotherapy is effective, but limited by toxicities to normal tissue and inability to treat systemically. Antibody pretargeting involves targeting of an antibody bearing a high affinity receptor such as streptavidin, clearing the remaining antibody-receptor in circulation after tumor uptake and finally delivery of radiation via a small molecule ligand (biotin). This decoupling of the targeting from the radiation delivery allows optimization of tumor targeting in a non-toxic step. The delivery of radiation on a small molecule results in rapid delivery of the radiation to the tumor as well as rapid urinary excretion of non-targeted radioactivity. These characteristics are ideal for application of high potency, short lived alpha emitter radionuclides such as Bismuth-212 from Lead-212. Reagents developed for pretargeting include the DOTA chelating agent which has been shown to chelate Lead-212. This research project will evaluate the ability of pretargeting reagents to effectively target 212Pb for in vivo generation of 212Bi alpha radiotherapy. The chelation of 212Pb and 212Bi by DOTA- biotin and in vivo tumor targeting of these radionuclides will be determined. Realization of this goal of this project will allow application of high potency alpha particle radiotherapy to effectively and selectively treat solid tumors. PROPOSED COMMERCIAL APPLICATION The use of highly potent alpha emitters in cancer therapy has been limited to easily accessible tumor cells such as those in leukemia due to their short half lives and short path lengths. Pretargeting and alpha emitters may enable more effective treatment of solid tumors such as breast, lung, colon and prostate carcinomas. These cancers represent a very large market opportunity for the development of more effective treatments.